! Regional Anesthesia and Anticoagulation: A Comprehensive Guide

! Introduction and Welcome

''Who is conducting this session and what is the topic?''

Dr. Anisha, Assistant Professor at Comm Academy of Medical Sciences and Research Center, is welcoming everyone to the ISA National PG online classes. The topic of discussion for the day is "Regional anesthesia and anticoagulation."

''What is the context and importance of this topic?''

Dr. Sukender Baja, Honorary Secretary of ISA National, introduces the topic, stating that after the age of 40, almost every fifth person is on an anticoagulant. Postgraduate students frequently face dilemmas during preanesthetic checkups regarding when to stop these medications, for how many days, and how to weigh the pros and cons for surgery, especially for patients who have had cardiac surgery or are on various comorbidities. This makes the perioperative period potentially stormy, and the topic is relevant for everyday practice, teaching, and theoretical purposes.

''Who are the key faculty members and their roles?''

The session is introduced by Dr. Manasvini, who presents the faculty: - **Dr. M. Vam sir:** Professor and HOD, with 26 years of teaching experience and an interest in Regional anesthesia. - **Dr. Vidita K:** Professor, with 9 years of PG teaching experience. - **Dr. Lakshmi Priyanka:** Professor, with 8 years of experience and a special interest in ultrasound-guided regional anesthesia. - **Dr. Sur Kumar:** Chief Cardiac Anesthesiologist. - **Dr. Anusha:** Assistant Professor.

''What are the instructions for the participants?''

Participants are requested to mute their audio and turn off their video during the session. All queries should be shared in the chat box and will be answered at the end of the session.

''What is the value of Regional Anesthesia?''

Regional anesthesia preserves respiratory function, reduces the risk of aspiration, offers better hemodynamic stability, reduces the use of anesthesia drugs, allows for quicker recovery, is less costly for the patient, and lowers the risk of deep vein thrombosis. It is particularly good for high-risk patients needing lower limb surgery, especially in orthopedics and obstetrics, and reduces overall healthcare costs.

! Case Presentation: A Patient on Anticoagulants for Hip Surgery

''What is the case being presented?''

Dr. Shishir, a third-year postgraduate, presents a case of an 80-year-old male, Mr. Raju, who had a fall resulting in an acetabular fracture of the left hip. He was posted for a left bipolar hemiarthroplasty.

''What are the patient's relevant medical history and medications?''

- **Cardiac History:** History of dyspnea on exertion (NYHA Grade III) for 6 months, unstable angina in 2023. Known case of Coronary Artery Disease (CAD) with PTCA to LAD in 2008 and PTCA to RCA in 2023. - **Other Conditions:** Type 2 Diabetes Mellitus (for 15 years) and Hypertension (for 15 years). - **Medications:** - Tablet Voglibose 50 mg BD and Metformin 500 mg BD (for diabetes) - Tablet Ramipril 2.5 mg OD (for hypertension) - Tablet Ecosprin 75 mg OD and Tablet Ticagrelor 90 mg OD (for CAD, since 1 year)

''What do the terms NYHA Grade III and Unstable Angina mean in this context?''

- **NYHA Grade III:** It signifies a marked limitation of physical activity. The patient is comfortable at rest, but less-than-ordinary activity (like climbing two flights of stairs) will cause fatigue, palpitation, or dyspnea. - **Unstable Angina:** This refers to angina pain that occurs with minimal activity or is increasing in frequency and severity but is not constant.

''What were the patient's physical examination and investigation findings?''

- **General Examination:** Lean built, conscious, oriented. No signs of pallor, icterus, clubbing, lymphadenopathy, or pedal edema. Edentulous with a normal tongue. Cervical and lumbar spine were normal. - **Vitals:** BP 130/80 mmHg, Pulse 70 bpm, SpO2 96% on room air. - **Airway:** TMD >6 cm, mouth opening 3 fingers, MP Grade II. - **Systemic Examination:** CVS and RS were normal. Per abdomen soft, non-tender. - **ECG:** T-wave inversions in V5 and V6 with no acute ST changes. - **2D Echo:** Concentric LVH, RWMA in inferior and posterior wall, Grade I diastolic dysfunction, mild TR, no PAH, EF 54%. - **Chest X-ray:** Cardiomegaly with aortic knuckle calcification. - **Laboratory:** Hb 12.7%, TLC 11,450, Platelets 2.4 lakhs, Urea 17, Sr. Creatinine 0.8, Na+ 135, K+ 4.3, RBS 175 mg/dL, PT 11.9 sec, INR 0.9, APTT 27.6 sec.

''What was the planned anesthetic management and the strategy for anticoagulation?''

- **Anesthesia Plan:** Combined Spinal and Epidural (CSE) anesthesia. - **Cardiology Consultation:** Patient was stratified as mild risk for non-cardiac surgery. - **Preoperative Medication Adjustments:** - **Ticagrelor:** Stopped 5 days prior to surgery. - **Bridging Therapy:** Started on Injection Heparin 5000 IU subcutaneous BD, which was stopped 6 hours prior to surgery. - **Ramipril:** Stopped on the day of surgery. - **Amlodipine:** 10 mg advised on the day of surgery. - **OHAs:** Stopped on the day of surgery. - **NBM:** From 12:00 a.m. midnight. - **Day of Surgery Coagulation Profile:** PT 12.3 sec, INR 1.02, APTT 39.8 sec.

''What precautions were taken during the administration of regional anesthesia in this anticoagulated patient?''

- **Single Attempt:** The epidural was placed in a single attempt to minimize the risk of bleeding and spinal/epidural hematoma. It is generally advised to minimize the number of pricks to less than three. - **Confirmation:** Epidural placement was confirmed by a fall in the column in the epidural catheter. - **Spinal Anesthesia:** A 25G Quincke Babcock spinal needle was used at L3-L4 level after confirming a backflow of clear CSF.

''What additional precautions and monitors were used intraoperatively?''

- **Monitors:** Baseline ECG, NIBP, and SpO2 were attached and checked in the operating theater. - **Difficult Airway Precautions:** As the patient was edentulous, there was a risk of difficult bag-mask ventilation. A difficult airway cart was kept ready, and care was taken to ensure a tight seal during mask ventilation. - **Plan B:** General anesthesia was prepared as a backup plan in case regional anesthesia was not feasible.

''How was the patient positioned for the block, and what alternative was considered?''

The patient was positioned for the CSE with his cooperation. An alternative considered was a Pericapsular Nerve Group (PENG) block to ease positioning for the procedure by reducing pain from the hip fracture, but it was deemed unnecessary as the patient cooperated well.

''What is the significance of the epidural space's anatomy in the context of bleeding?''

The anterior and lateral parts of the epidural space contain a rich venous plexus. Therefore, if a needle is advanced laterally or hits the anterior part of the column, the incidence of epidural hematoma is higher due to the risk of puncturing these veins.

''What was the postoperative management plan?''

- **Pain Management:** Postoperative pain was managed with an infusion of 0.125% Bupivacaine through the epidural catheter. - **Anticoagulation Resumption:** Heparin 5000 IU subcutaneous BD was resumed postoperatively. - **Catheter Removal:** The epidural catheter was removed on postoperative day 2, 6 hours after the last dose of Heparin. - **Ticagrelor Resumption:** Tablet Ticagrelor was resumed 6 hours after the catheter was removed.

''Do local anesthetics interfere with the coagulation process?''

As per the presenter's awareness, there are no reports suggesting that local anesthetics interfere with anticoagulants or antiplatelets.

!! Understanding Coagulation and Its Testing

''Can you briefly describe the coagulation cascade?''

The coagulation cascade consists of two main pathways that converge into a common pathway: - **Intrinsic Pathway:** Activated by contact with negatively charged surfaces (e.g., collagen). This activates Factor 12, then 11, 9, and 8, leading to the activation of Factor 10. - **Extrinsic Pathway:** Activated by tissue factor (from damaged tissue outside the blood vessel). This activates Factor 7, which then activates Factor 10. - **Common Pathway:** Activated Factor 10 converts prothrombin (Factor 2) to thrombin (Factor 2a). Thrombin then converts fibrinogen to fibrin. Factor 13 stabilizes the fibrin clot.

''What is the cell-based model of coagulation?''

This newer model emphasizes the role of damaged endothelial cells and has three phases: - **Initiation:** Occurs on tissue factor-bearing fibroblasts. The tissue factor and Factor 7a complex generates a small amount of Factor 9, 10, and thrombin. - **Amplification:** Happens on the surface of activated platelets, further activating them and releasing factors like von Willebrand factor. - **Propagation:** More platelets are recruited, and the intrinsic tenase complex (Factor 9a, 8a, phospholipids, calcium) and extrinsic tenase complex (tissue factor, 7a, phospholipids, calcium) form a prothrombinase complex, leading to a burst of thrombin and stable clot formation.

''What does PT and INR measure?''

PT (Prothrombin Time) and INR (International Normalized Ratio) measure the **extrinsic and common pathways** of coagulation. The test involves adding tissue factor to a plasma sample and measuring the time to clot. It is most sensitive to Factor 7, a vitamin K-dependent factor with a short half-life. An INR of 1.5 is the usual cutoff for neuraxial procedures, as it is associated with normal coagulation.

''What does APTT measure?''

APTT (Activated Partial Thromboplastin Time) measures the **intrinsic and common pathways**. The test uses a "partial" thromboplastin (phospholipid only, no tissue factor) and a negatively charged substance (like silica) to activate the intrinsic pathway. It is useful for monitoring unfractionated heparin and detecting acquired hemophilia.

''What minimum percentage of coagulation factors is needed for normal hemostasis?''

At least 40-50% of coagulation factors should be intact for normal coagulation to take place. If a patient is bleeding, it usually means the clotting factors are deficient to less than 30%.

!! Anticoagulant and Antiplatelet Drugs: A Pharmacological Overview

''How are anticoagulant drugs classified?''

Anticoagulants are broadly classified into parenteral and oral drugs. - **Parenteral:** - **Indirect Thrombin Inhibitors:** Unfractionated Heparin, Low Molecular Weight Heparin (LMWH, e.g., Enoxaparin), and Fondaparinux. - **Direct Thrombin Inhibitors:** Bivalirudin, Argatroban, Lepirudin. - **Oral:** - **Vitamin K Antagonist:** Warfarin. - **Direct Factor 10a Inhibitors:** Rivaroxaban, Apixaban, Edoxaban. - **Direct Thrombin Inhibitors:** Dabigatran.

''What is the mechanism of action of Warfarin and why does its onset/offset take several days?''

Warfarin exerts its anticoagulant effect by interfering with the synthesis of vitamin K-dependent clotting factors (Factors 2, 7, 9, 10) and the anticoagulant proteins C and S. - **Onset:** INR prolongation is seen within 24-72 hours, but a peak therapeutic effect takes 5-7 days. The initial INR is unreliable due to the competing depletion of procoagulant (Factor 7) and anticoagulant (Protein C) factors. - **Offset:** It takes several days for the body to synthesize new, functional vitamin K-dependent clotting factors after Warfarin is stopped.

''What are the key differences between Unfractionated Heparin (UFH) and Low Molecular Weight Heparin (LMWH)?''

- **Mechanism:** Both activate Antithrombin 3. UFH inhibits Factors 2a, 10a, 9a, 11a, and 12a. LMWH primarily inhibits Factor 10a. - **Administration:** UFH is intravenous; LMWH is subcutaneous. - **Half-life:** UFH: 1.5-2 hours; LMWH: 3-6 hours; Fondaparinux: 17-21 hours. - **Reversal:** UFH is rapidly reversed by Protamine sulfate. LMWH is only partially reversible by Protamine. - **Monitoring:** UFH requires therapeutic monitoring (APTT). LMWH does not. - **Side Effects:** UFH has a higher risk of Heparin-Induced Thrombocytopenia (HIT) and osteoporosis compared to LMWH. Fondaparinux has no risk of HIT. - **Renal Failure:** UFH is preferred in renal failure (GFR <30). LMWH should be avoided or used with caution.

''What are Direct Oral Anticoagulants (DOACs) and what are their advantages over Warfarin?''

DOACs include Dabigatran (direct thrombin inhibitor) and Rivaroxaban, Apixaban, Edoxaban (Factor 10a inhibitors). Their advantages include: - Predictable therapeutic response (no routine monitoring required). - Rapid onset of action. - Fewer drug interactions. - Bridging therapy is often not required.

''What is a key consideration for Dabigatran?''

Dabigatran has 80% renal excretion, so its dosing and timing must be carefully adjusted in patients with renal impairment.

''How are antiplatelet drugs classified by mechanism of action?''

- **COX Inhibitors:** Aspirin (inhibits Thromboxane A2). - **ADP Receptor (P2Y12) Antagonists:** Irreversible (Clopidogrel, Prasugrel) and Reversible (Ticagrelor, Cangrelor). - **Phosphodiesterase Inhibitors:** Dipyridamole, Cilostazol. - **Glycoprotein IIb/IIIa Inhibitors:** Tirofiban, Eptifibatide, Abciximab (intravenous).

''What is unique about the reversible ADP receptor antagonists?''

Ticagrelor and Cangrelor are reversible P2Y12 antagonists. A key clinical point is that if platelets are transfused to reverse their effect, the drug in the plasma can immediately block the newly transfused platelets, making platelet transfusion less efficient for up to 24 hours after the last dose of Ticagrelor.

! ASRA Guidelines and Implications for Regional Anesthesia

''What is ASRA and why are its guidelines important?''

ASRA stands for the American Society of Regional Anesthesia and Pain Medicine. These guidelines are crucial as they provide recommendations on managing anticoagulation, antithrombotic, and thrombolytic agents in patients receiving regional anesthesia, primarily to prevent bleeding complications like neuraxial hematoma.

''What are the key principles behind the timing of drug cessation and restart for neuraxial procedures?''

- **Five Half-Lives:** For therapeutic anticoagulation, a time interval of five half-lives is recommended before a neuraxial block to allow for a 97% resolution of the anticoagulant effect. This is dependent on renal function and patient comorbidities. - **Two Half-Lives:** For prophylactic anticoagulation, a two half-life interval is suggested. - **Eight-Hour Rule (Rosener et al.):** A platelet plug takes about 8 hours to become stable. Subsequent dosing of antithrombotics should be timed considering this window minus the drug's time to peak effect.

''How are ASRA recommendations graded?''

- **Grade 1:** General agreement on efficacy ("recommend"). - **Grade 2:** Conflicting evidence or opinion on usefulness ("suggest," requiring clinical judgment). - **Grade 3:** Not typically used in these guidelines.

''What is spinal hematoma and how common is it?''

Spinal hematoma is symptomatic bleeding within the neuraxial axis. While a very rare complication, it is catastrophic when it occurs. The incidence is approximately 1 in 150,000 for epidurals and 1 in 220,000 for spinals. Bleeding most commonly occurs in the epidural space due to its prominent venous plexus.

''What are the risk factors and presenting symptoms of spinal hematoma?''

- **Risk Factors:** Clotting abnormalities, difficulty in needle/catheter placement, a bloody tap, and vascular surgery. Importantly, 60% of cases in one review occurred in the last decade, likely due to increased anticoagulant use. Catheter removal is also a critical time, with 32 of 61 cases developing hematoma immediately after removal. - **Symptoms:** Progressive sensory or motor block (beyond what is expected from the local anesthetic) is the most common presentation. Back pain is not a reliable symptom. Bladder or bowel dysfunction may occur later.

''How is spinal hematoma diagnosed and managed?''

- **Diagnosis:** High index of suspicion is key. Use low-concentration local anesthetics for postoperative infusions to allow for easy detection of a new or progressive motor block. MRI is the imaging modality of choice. - **Management:** If a hematoma is suspected, immediate neurological consultation is required. Surgical intervention (laminectomy) within 8 hours of the onset of neurological dysfunction is critical for a good neurological recovery.

''What are the ASRA recommendations for patients on thrombolytics?''

Neuraxial procedures should generally be avoided in patients who have received thrombolytics. If a procedure has been performed, a 10-day waiting period is advised, and frequent neurological monitoring is essential.

''What are the key recommendations for common anticoagulants before neuraxial procedures?''

- **Aspirin:** No restriction. - **Clopidogrel:** Withhold for 5-7 days. - **Warfarin:** Discontinue 5 days prior, check INR (should be normal or <1.5). - **UFH (prophylactic/subcutaneous):** No contraindication, but delay for 4-6 hours and check APTT if on long-term therapy. - **UFH (therapeutic/IV):** Withhold for 4-6 hours, check APTT normal before block. - **LMWH (prophylactic):** Withhold for 12 hours. - **LMWH (therapeutic):** Withhold for 24 hours. - **Fondaparinux:** Avoid neuraxial techniques due to its long half-life and lack of reversal. - **Direct Thrombin Inhibitors (e.g., Argatroban, Bivalirudin):** Avoid neuraxial techniques. - **DOACs (Rivaroxaban, Apixaban, Dabigatran):** It is better to avoid neuraxial catheters. Cessation times vary (e.g., Rivaroxaban 72 hours, Dabigatran depends on renal function 48-96 hours).

''What is a crucial take-home point regarding the use of guidelines?''

Do not blindly follow guidelines. They must be used in conjunction with sound clinical judgment. If the risk of bleeding is high, consider alternatives to neuraxial techniques, such as peripheral nerve blocks (especially superficial ones) or IV medications.

! Regional Anesthesia in Cardiac Surgery: A Special Context

''Is it safe to perform fascial plane blocks in cardiac surgery patients on anticoagulants?''

A 2022 retrospective study in the Journal of Cardiothoracic and Vascular Anesthesia suggested that continuous erector spinae plane (ESP) blocks and serratus anterior plane (SAP) blocks were performed without major adverse effects, even in the presence of anticoagulation. Many patients had blocks placed and catheters removed with INR >1.4, low platelets, or while on therapeutic LMWH, with no attributable major complications.

''What are the potential benefits of neuraxial anesthesia in cardiac surgery?''

Meta-analyses have shown that adding thoracic epidural analgesia to general anesthesia for cardiac surgery may lead to: - Decreased incidence of acute renal failure. - Decreased mechanical ventilation time. - Decreased supraventricular tachycardia and respiratory complications. - Reduced ICU and hospital stay. - No difference in mortality, MI, or stroke. - **Physiological benefit:** Sympatholysis (T1-T4) can provide coronary vasodilation, decrease stress response, and reduce myocardial oxygen demand.

''What are the specific concerns with neuraxial anesthesia in cardiac surgery patients?''

- **Full Heparinization:** The need for full anticoagulation for cardiopulmonary bypass (CPB) significantly increases the risk of epidural hematoma. - **Post-CPB Coagulopathy:** The risk is compounded by the coagulopathy that can occur after bypass. - **Dual Antiplatelet Therapy:** Many cardiac patients are on dual antiplatelet therapy (e.g., aspirin + P2Y12 inhibitor). - **Estimated Risk:** The estimated risk of epidural hematoma in this setting is higher, around 1 in 5,493 cases based on some data.

''What are the recommended precautions if neuraxial techniques are used in cardiac surgery?''

- **Timing:** Delay systemic heparinization for at least 60-120 minutes after neuraxial instrumentation. Some practitioners place the catheter the day before surgery. - **Traumatic Tap:** In the event of a bloody or traumatic tap, surgery should be delayed for 24 hours. - **Heparin Dose:** Administer the smallest effective dose of heparin for the shortest duration possible. - **Catheter Removal:** Remove the epidural catheter only after normal coagulation has been confirmed postoperatively. - **Monitoring:** Continue close neurological monitoring for signs of hematoma.

''What is the bottom line regarding neuraxial anesthesia for cardiac surgery?''

Due to the small but potentially devastating risk of epidural hematoma, its use remains controversial. Optimal patient selection is paramount, weighing the risks of hematoma and hemodynamic instability against the potential benefits. Thoughtful multimodal analgesic regimens, including fascial plane blocks, should also be considered.

! Summary and Key Takeaways from the Session

''What is the most crucial advice for a postgraduate student when dealing with these patients?''

Always take a thorough history, not just for conventional anticoagulants but also for over-the-counter and alternative therapies (Ayurvedic, Homeopathic, Unani) which can impact coagulation. Have a checklist for signs of bleeding disorders. Base decisions on a balance between the risk of thromboembolism and the risk of bleeding. Use guidelines, but apply your clinical judgment.

''What is the concept of and need for 'ISRA' guidelines?''

Dr. Baja proposed the development of Indian Society of Regional Anesthesia (ISRA) guidelines. The rationale is that India has a unique population with varied dietary and cultural practices, and a high prevalence of alternative medicine use (Ayurvedic, Unani, etc.). These agents can significantly interfere with coagulation but are rarely reported or accounted for in Western guidelines. Collecting data and experiences from Indian patients would lead to more relevant and impactful guidelines for the local context.